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Pulmonary neuroendocrine cells: physiology, tissue homeostasis and disease.

ABSTRACT: Mammalian lungs have the ability to recognize external environments by sensing different compounds in inhaled air. Pulmonary neuroendocrine cells (PNECs) are rare, multi-functional epithelial cells currently garnering attention as intrapulmonary sensors; PNECs can detect hypoxic conditions through chemoreception. Because PNEC overactivation has been reported in patients suffering from respiratory diseases - such as asthma, chronic obstructive pulmonary disease, bronchopulmonary dysplasia and other congenital diseases - an improved understanding of the fundamental characteristics of PNECs is becoming crucial in pulmonary biology and pathology. During the past decade, murine genetics and disease models revealed the involvement of PNECs in lung ventilation dynamics, mechanosensing and the type 2 immune responses. Single-cell RNA sequencing further unveiled heterogeneous gene expression profiles in the PNEC population and revealed that a small number of PNECs undergo reprogramming during regeneration. Aberrant large clusters of PNECs have been observed in neuroendocrine tumors, including small-cell lung cancer (SCLC). Modern innovation of imaging analyses has enabled the discovery of dynamic migratory behaviors of PNECs during airway development, perhaps relating to SCLC malignancy. This Review summarizes the findings from research on PNECs, along with novel knowledge about their function. In addition, it thoroughly addresses the relevant questions concerning the molecular pathology of pulmonary diseases and related therapeutic approaches.

SUBMITTER: Noguchi M

PROVIDER: S-EPMC7774893 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Pulmonary neuroendocrine cells: physiology, tissue homeostasis and disease.

Noguchi Masafumi M Furukawa Kana T KT Morimoto Mitsuru M

Disease models & mechanisms 20201221 12

Mammalian lungs have the ability to recognize external environments by sensing different compounds in inhaled air. Pulmonary neuroendocrine cells (PNECs) are rare, multi-functional epithelial cells currently garnering attention as intrapulmonary sensors; PNECs can detect hypoxic conditions through chemoreception. Because PNEC overactivation has been reported in patients suffering from respiratory diseases - such as asthma, chronic obstructive pulmonary disease, bronchopulmonary dysplasia and oth ...[more]

PMID: 33355253

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Project description:Compelling evidence in rats support the idea that gestational chronodisruption induces major changes in maternal circadian rhythms and fetal development and that these changes impact adult life at many physiological levels. Using a model of chronic photoperiod shifting throughout gestation (CPS), in which pregnant female rats (Sprague-Dawley strain; n = 16 per group) were exposed to lighting schedule manipulation every 3-4 days reversing the photoperiod completely or light/dark photoperiod (12/12; LD), we explored in the adult rat male offspring body weight gain, glucose homeostasis, adipose tissue content, adipose tissue response to norepinephrine (NE), and adipose tissue proteomic in the basal condition with standard diet (SD) and in response to high-fat diet (HFD). In adult CPS male (100-200 days old; n = 8 per group), we found increasing body weight, under SD and adiposity. Also, we found an increased response to intraperitoneal glucose (IGTT). After 12 weeks of HFD, white adipose tissue depots in CPS offspring were increased further, and higher IGTT and lower intraperitoneal insulin tolerance response were found, despite the lack of changes in food intake. In in vitro experiments, we observed that adipose tissue (WAT and BAT) glycerol response to NE from CPS offspring was decreased, and it was completely abolished by HFD. At the proteomic level, in CPS adipose tissue, 275 proteins displayed differential expression, compared with LD animals fed with a standard diet. Interestingly, CPS offspring and LD fed with HFD showed 20 proteins in common (2 upregulated and 18 downregulated). Based on these common proteins, the IPA analysis found that two functional pathways were significantly altered by CPS: network 1 (AKT/ERK) and network 2 (TNF/IL4; data are available via ProteomeXchange with identifier PXD026315). The present data show that gestational chronodisruption induced deleterious effects in adipose tissue recruitment and function, supporting the idea that adipose tissue function was programmed in utero by gestational chronodisruption, inducing deficient metabolic responses that persist into adulthood.

Dataset Information

Pulmonary neuroendocrine cells: physiology, tissue homeostasis and disease.

Publications

Pulmonary neuroendocrine cells: physiology, tissue homeostasis and disease.

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